Dataset Information

Wntless regulates dentin apposition and root elongation in the mandibular molar.

ABSTRACT: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, leads to severe defects in dentin formation and root elongation. Dentin thickness decreased remarkably and pulp chambers enlarged in the mandibular molars of OC-Cre;Wls(CO/CO) mice. Although the initial odontoblast differentiation was normal in the mutant crown, odontoblasts became cuboidal and dentin thickness was reduced. In immunohistochemistry, Wnt10a, ?-catenin, type I collagen, and dentin sialoprotein were significantly down-regulated in the odontoblasts of mutant crown. In addition, roots were short and root canals were widened. Cell proliferation was reduced in the developing root apex of mutant molars. Furthermore, Wnt10a and Axin2 expression was remarkably decreased in the odontoblasts of mutant roots. Deletion of the Wls gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation and root elongation.

SUBMITTER: Bae CH

PROVIDER: S-EPMC4814015 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Wntless regulates dentin apposition and root elongation in the mandibular molar.

Bae C H CH Kim T H TH Ko S O SO Lee J C JC Yang X X Cho E S ES

Journal of dental research 20150116 3

Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, leads to severe defects in dentin formation and root elongation. Dentin thickness decreased remarkably and pulp chamber ...[more]

PMID: 25595365

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Project description:Tooth development is a complex process that is regulated precisely by several signalling pathways and transcription factors. GATA-binding protein 4 (GATA4) is a DNA binding transcription factor, and our previous study showed that GATA4 is a novel regulator of root development. However, it remains unclear whether GATA4 is necessary for odontoblast differentiation and dentin formation. Here, we evaluated the phenotypic changes of Wnt1-Cre;GATA4fl/fl mice. The mutant mice showed defective dentin and short root deformity. The odontoblasts lost polarity instead of exhibiting a shorter height and flattened morphology. Moreover, the expression of several molecules, such as DSPP, COL-1, DCN, and PCNA, were downregulated during mutant tooth development. In vivo, we injected lentivirus to overexpress GATA4 in mice root. The dentin formation and the expression of odonto/osteogenic markers (DSPP, COL-1, DCN) were enhanced in the GATA4 overexpression group. During the in vitro study, the ability of proliferation, migration and odonto/osteogenic differentiation was declined by GATA4 knockdown approach in human dental pulp stem cells (DPSCs). The expression of odonto/osteogenic markers (DSPP, BMP4, RUNX2, OSX, OPN, OCN) was reduced in the shGATA4 group, while overexpressing GATA4 in DPSCs promoted mineralization. Furthermore, an immunoprecipitation-mass spectrometry procedure was used to confirm the interaction between GATA4 and Fructose-1, 6-bisphosphatase 1 (FBP1). We used gain and lose-of-function to delineated the role of GATA4 in regulating FBP1 expression. Knocking down GATA4 in DPSCs resulted in decreased glucose consumption and lactate production. We used small hairpin RNA targeting FBP1 to reduce the expression of FBP1 in DPSCs, which significantly increased glucose consumption and lactate production. Together, the results suggested that GATA4 is important for root formation and odontoblast polarity, as it promotes the growth and differentiation of dental mesenchymal cells around the root and affects the glucose metabolism of DPSCs via the negative regulation of FBP1.

Project description:ABSTRACT Context: In the present era of allopathic medication usage, there is always a risk of toxicity. Turmeric is a wonderful natural herb with excellent healing properties and a plethora of many clinical trials in dentistry. Hence, this study aims to evaluate the efficacy of healing in mandibular molar extraction sockets with and without turmeric gel. Aim: This study aimed to evaluate the efficacy of turmeric gel with the objective of analyzing the soft tissue healing in mandibular molar extraction sockets with and without turmeric gel. Settings and Design: The split-mouth study design with randomization of the sites was done using the sequentially numbered opaque sealed envelope (SNOSE) in the same patient indicated for bilateral lower molar extraction. A total of 50 patients were included in the study, who were divided into group A, 25 patients in the experimental site using turmeric gel, and group B, 25 patients in the control site without turmeric gel. Materials and Methods: Turmeric in the form of gel was used in the experimental site to evaluate its efficacy in soft tissue healing of the mandibular molar extraction socket. The extraction sites of the same patient were evaluated for soft tissue healing on postoperative day 1, day 7, and day 21 using Landry, Turn Bell, and Howley scale. Statistical Analysis: A comparison of soft tissue healing between group A and group B, which showed a consequential difference in group A on day 7 with P = 0.001 and day 21 with P = 0.001, was significant. Results: Results revealed postoperative day 1 showed a significant beginning of healthy granulation tissue formation in both the groups. There was a consequential difference in soft tissue healing in group A on postoperative day 7 and day 21 as compared to group B. The turmeric in the form of gel proved to enhance the soft tissue healing in the mandibular molar extraction socket. Conclusions: The present study revealed that enhanced soft tissue healing of the extraction socket of the mandibular molar was present in the turmeric gel group on postoperative day 7 and day 21 than in without the turmeric gel group.

Dataset Information

Wntless regulates dentin apposition and root elongation in the mandibular molar.

Publications

Wntless regulates dentin apposition and root elongation in the mandibular molar.

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